The neuroprotective activity of 8-alkylamino-1,4-benzoxazine antioxidants

Autor: Alain Le Ridant, Martine Largeron, Michael Spedding, Bettina Mesples, Roméo Cecchelli, Pierre Gressens, Maurice-Bernard Fleury
Přispěvatelé: Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), Neuroscience et Pharmacologie, Institut de Recherches Servier, Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Déplanques, Wilfried
Jazyk: angličtina
Rok vydání: 2001
Předmět:
Pathology
Antioxidant
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Pharmacology
Antioxidants
Mice
0302 clinical medicine
Alkylamino-1
Adenosine Triphosphate
Medicine
ComputingMilieux_MISCELLANEOUS
0303 health sciences
Alanine
Brain
Biological activity
Neuroprotection
3. Good health
Dose–response relationship
4-benzoxazine
medicine.anatomical_structure
Neuroprotective Agents
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
medicine.symptom
Astrocyte
medicine.medical_specialty
Brain damage
03 medical and health sciences
Benzophenones
In vivo
Oxazines
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
030304 developmental biology
Dose-Response Relationship
Drug
business.industry
In vitro
Benzoxazines
Rats
Oxygen
Animals
Newborn
Astrocytes
Cerebral palsy
business
030217 neurology & neurosurgery
Leukomalacia
Zdroj: European Journal of Pharmacology
European Journal of Pharmacology, Elsevier, 2001, 424 (3), pp.189-194. ⟨10.1016/S0014-2999(01)01152-9⟩
European Journal of Pharmacology, Elsevier, 2001, 424, p. 189-194
ISSN: 0014-2999
DOI: 10.1016/S0014-2999(01)01152-9⟩
Popis: International audience; Antioxidant 8-alkylamino-1,4-benzoxazines, (R,S)-(3-tert-butyl-8-phenylethylamino-3,4-dihydro-2H-1,4-benzoxazin-5-yl) (phenyl) methanone (S 24429) and (R,S)-(3-cyclopentyl-8-benzylamino-3,4-dihydro-2H-1,4-benzoxazin-5-yl) (phenyl) methanone (S 24718), were prepared according to a two-step one-pot electrochemical procedure. These compounds had been selected from a previous study of structure / activity. Both compounds (1–100 μM) prevented the fall in ATP levels caused by 24 h of hypoxia in astrocytes. Both compounds (1 and 10 mg/kg i.p.) were powerful neuroprotective agents in protecting against the lesions induced by 15 mg S-bromo-willardiine injected into the cortex or white matter of 5-day old mice pups. In contrast, exifone, an antioxidant compound, was inactive at these doses. S 24429 and S 24718 appear to be novel neuroprotective agents, which are effective in a model of brain damage mimicking the lesions underlying cerebral palsy.
Databáze: OpenAIRE
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